Project description:Collectively, viruses are the principal cause of cancers arising in patients with immune dysfunction, including HIV+ patients. Kaposi’s Sarcoma (KS) etiologically linked to KSHV continues to be the most common AIDS-associated tumor. The involvement of oral cavity represents one of the most common clinical manifestations of this tumor. HIV infection incurs an increased risk for periodontal diseases and oral carriage from a variety of pathogenic bacteria. In the current study, by using 16S rRNA based pyrosequencing, we found that oral shedding of KSHV altered oral microbiota signature in HIV+ patients which may contribute to virus-associated malignancies development.
Project description:Kaposi's Sarcoma (KS) caused by Kaposi's sarcoma-associated herpesvirus (KSHV) continues to be the most common AIDS-associated tumor. Involvement of the oral cavity represents one of the most common clinical manifestations of this tumor. Numerous types of cancer are associated with the alterations of in components of the microbiome. However, little is known about how KSHV coinfection affects the oral microbiome in HIV+ patients, especially in a "pre-cancer" niche. Using 16S rRNA pyrosequencing, we found that oral shedding of KSHV correlated with altered oral microbiome signatures in HIV+ patients, including a reduction in the microbiota diversity, changing the relative composition of specific phyla and species, and regulating microbial functions. Furthermore, we found that Streptococcus sp., one of the most increased species in the oral cavity of HIV+/KSHV+ patients, induced KSHV lytic reactivation in primary oral cells. Together, these data indicate that oral shedding of KSHV may manipulate the oral microbiome to promote viral pathogenesis and tumorigenesis especially in immunocompromised patients.
Project description:Purpose: The goal of this study is to compare the transcriptomic profiles of healthy individuals and HIV+ patients on therapy Methods: Cells were pelleted from gingival mucosa. mRNA profiles were generated by Next-gen sequencing using the Illumina platform. Results: Comprehensive transcriptome data that showed underlying changes in the oral mucosal immune system of HIV+ patients on therapy. The transcriptome data of the pooled healthy controls are presented here. Conclusions: Our study represents the analysis of oral gingival transcriptomes. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biological functional alterations during chronic viral infections such as HIV infection.
Project description:Progestin-based contraception may increase the risk of vaginal HIV acquisition to a level greater than the progesterone-rich luteal phase of the menstrual cycle, which has been demonstrated to have a significantly higher transmission rate compared to the follicular phase. We used pig-tailed macaque (Macaca nemestrina) model to evaluate the effects of administration of the oral the combined oral contraceptives (COCs) depot medroxyprogesterone acetate (DMPA) and levonorgestrel (LNG) on mucosal factors that influence HIV susceptibility. We compared the pH and vaginal epithelial thickness data from previous studies, and evaluated contraception-induced molecular changes in the vagina using transcriptional and cytokine profiling. The administration of DMPA caused a pronounced thinning of the vaginal epilthelium relative to measurements takein in the follicular or luteal phase. DMPA also induced a significant increase in vaginal IL10 expression. Lastly, using RNA-Seq analyses of vaginal biopsies, we noted that both DMPA- and LNG-based contraception induced a signature of gene expression similar to that of the luteal phase, only more exacerbated, and including widespread down-regulation of HIV-restriction genes. Use of progestin-based contraception might engender a milieu that poses an increased risk of HIV transmission than that of the luteal phase via vaginal thinning, induction of immunosuppressive cytokines, and widespread suppression of HIV restriction factors.
Project description:Proteomic analysis of cytokines in unstimulated oropharyngeal secretions. Epstein-barr virus (EBV) is a type 1 carcinogen which causes many cancers in humans. Here we explored the cytokine involvement of the EBV replication process in the oropharynx. Cytokine interactomic profiles were geneerated to understand the involved signalling pathways in HIV infected group and the healthy group. Proteome profilers were used to understand the major cytokine expression levels that are related to infection and immune regulation. We analyzed unstimulated oropharyngeal samples (UOPS) from 42 healthy subjects and 72 HIV positive subjects using the R & D Proteome Profiler array panels. No techinical replicates were performed. 14 samples in HIV group without therapy (NHAART group); 58 HIV patients with highly active antiretroviral therapy (HAART group); 42 samples in healthy group
Project description:To study characteristics of the orapharyngeal epithelia which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil and gingival epithelium.Tonsil epithelium has been implicated in HIV pathogenesis, but its role in oral transmission remains controversial. We performed microarray analysis of Laser Capture Microdissected tonsil and gingival epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared to the epithelium of another oro-pharyngeal site, gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV binding molecules, FcRγIII, complement receptor 2, and various complement components. This increased expression of molecules involved in viral recognition, binding and entry may favor virus-epithelium interaction in an environment with reduced innate anti-viral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate anti-viral factors may render the tonsil a potential site for oral transmission. Keywords: Cross sectional
Project description:Systemic and local (oral mucosal) immune responses in acutely infected HIV individuals before the initiation of HAART have not been well characterized. Protein microarrays were used to analyze saliva and plasma from HIV infected and HIV uninfected subjects to identify new biomarkers for HIV disease progression and pathogenesis.